Lack of Site-Specific Production of Decidual Alpha-2 Macroglobulin in Human Pregnancy

Abstract

Background: Alpha-2 Macroglobulin (A2M) is a protease inhibitor that is present in both human and rat decidual tissue. In mice, decidual A2M prevents excessive trophoblastic invasion; however, its role in human decidual tissue is unknown. It is possible that A2M may also influence trophoblast invasion in human pregnancy, which would be reflected in increased A2M production in decidua basalis. The aim of the current study was to determine and compare A2M production from first trimester human decidua basalis and decidua parietalis.

Methods: Human decidual tissues were obtained from patients undergoing surgical termination at 9 to 12 gestational weeks. Strips of decidua basalis and decidua parietalis were obtained by uterine curettage under real-time ultrasound guidance. Tissue samples were fixed in 10% formalin or snap-frozen for immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, respectively. Protein and mRNA production between the two sites were compared using the Mann-Whitney U test.

Results: Paired basal and parietal decidua were analyzed by immunohistochemistry (n = 9) and by RT-PCR (n = 10). There was no significant difference in A2M mRNA expression between decidua basalis and decidua parietalis (P = .5). Immunohistochemical staining intensity for A2M protein was significantly higher in basalis than in parietalis (P = .004), but the extent of positively stained cells were not significantly different (P = .51). Strong A2M staining in decidua basalis was mainly localized in the intracellular storage vesicles, which may suggest a role of A2M in this site.

Conclusions: We conclude that the expression pattern of A2M in human decidua basalis and decidua parietalis is not consistent with an important role of this gene during the observed gestational period. Contrary to its role in rodent implantation, A2M is probably not involved in regulating human implantation and trophoblastic invasion during this gestational window frame.

Keywords

Alpha-2 macroglobulin deciduas pregnancy human

Get full access to this article

View all access options for this article.

References

1. Burton GJ , Jauniaux E . Placental oxidative stress: From miscarriage to preeclampsia. J Soc GGynecol Investig 2004;11:342-352.

2. Merviel P , Carbillon L , Challier JC , Rabreau M , Beaufils M , Uzan S . Pathophysiology of preeclampsia: Links with implantation disorders. Eur J Obstet Gynecol Reprod Biol 2004;115:134-147.

3. Kaufmann P , Black S , Huppertz B . Endovascular trophoblast invasion: Implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod 2003;69:1-7.

4. Myatt L . Role of placenta in preeclampsia. Endocrine 2002;19:103-111.

5. Goldman-Wohl D , Yagel S . Regulation of trophoblast invasion: From normal implantation to pre-eclampsia. Mol Cell Endocrinol 2002;187:233-238.

6. Floridon C , Nielsen O , Holund B , et al. Does plasminogen activator inhibitor-1 (PAI-1) control trophoblast invasion? A study of fetal and maternal tissue in intrauterine, tubal and molar pregnancies. Placenta 2000;21:754-762.

7. Staun-Ram E , Goldman S , Gabarin D , Shalev E . Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion. Reprod Biol Endocrinol 2004;2:59-59.

8. O'Shea JD , Kleinfeld RG , Morrow HA . Ultrastructure of decidualization in the pseudopregnant rat. Am J Anat 1983;166:271-298.

9. da Silva GC . Teixeira N , Bell SC . Major secretory product of the mesometrial decidua in the rat, a variant of alpha-2-macroglobulin, binds insulin-like growth factor I via a protease-dependent mechanism. Mol Reprod Dev 1996;44:103-110.

10.

10. Gu Y , Jayatilak PG , Parmer TG , Gauldie J , Fey GH , Gibori G . α2-Macroglobulin expression in the mesometrial decidua and its regulation by decidual luteotropin and prolactin. Endocrinology 1992;131:1321-1328.

11.

11. von Rango U , Classen-Linke I , Raven G , Bocken F , Beier HM . Cytokine microenvironments in human first trimester decidua are dependent on trophoblast cells. Fertil Steril 2003;79:1176-1186.

12.

12. Sindram-Trujillo AP , Scherjon SA , van Hulst-van Miert PP , et al. Differential distribution of NK cells in decidua basalis compared with decidua parietalis after uncomplicated human term pregnancy. Hum Immunol 2003;64:921-929.

13.

13. Choy MY , Sin SS , Leung TN , Lau TK . Human decidual production of hepatocyte-growth factor is not influenced by trophoblastic invasion in vivo. Fertil Steril 2004;82 (Suppl 3):1220-1225.

14.

14. Morimitsu Y , Hsia CC , Kojiro M , Tabor E . Nodules of less-differentiated tumor within or adjacent to hepatocellular carcinoma: Relative expression of transforming growth factor-alpha and its receptor in the different areas of tumor. Hum Pathol 1995;26:1126-1132.

15.

15. Blennow K , Ricksten A , Prince JA , et al. No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression. J Neural Transm 2000;107:1065-1079.

16.

16. Schlembach D . Pre-eclampsia—Still a disease of theories. Fukushima J Med Sci 2003;49:69-115.

17.

17. Cross JC . The genetics of pre-eclampsia: A feto-placental or maternal problem? Clin Genet 2003;64:96-103.

18.

18. Coukos G , Gafvels Me , Wisel S , et al. Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and the 39-kd receptor-associated protein in human trophoblasts. Am J Pathol 1994;144:383-392.

19.

19. Choy MY , Siu N , Leung TN , Lau TK . Unique in vitro expression of transforming growth factor beta-3 and alpha 2-macroglobulin in extravillous trophoblasts. Placenta 2002;23:A29-A29.

20.

20. Tayade C , Esadeg S , Fang Y , Croy BA . Functionsof alpha 2 macroglobulins in pregnancy. Mol Cell Endocrinol 2005;245:60-66.

21.

21. Murai M , Aramaki Y , Tsuchiya S . Alpha 2-macroglobulin stimulation of protein tyrosine phosphorylation in macrophages via the mannose receptor for Fc gamma receptor-mediated phagocytosis activation. Immunology 1996;89:436-441.

22.

22. Legres LG , Pochon F , Barray M , Gay F , Chouaib S , Delain E . Evidence for the binding of a biologically active interleukin-2 to human alpha 2-macroglobulin. J Biol Chem 1995;270:8381-8384.

23.

23. Valentin-Weigand P , Taore MY , Blobel H , Chhatwal GS . Role of alpha 2-macroglobulin in phagocytosis of group A and C streptococci. FEMS Microbiol Lett 1990;58:321-324.

24.

24. Esadeg S , He H , Pijnenborg R , Van Leuven F , Croy BA . Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation sites. Placenta 2003;24:912-921.

25.

25. Sayegh RA , Tao XJ , Leykin L , Isaacson KB . Endometrial alpha-2 macroglobulin; localization by in situ hybridization and effect on mouse embryo development in vitro. J Clin Endocrinol Metab 1997;82:4189-4195.

26.

26. Goldenberg RL , Tamura T , Cliver SP , Cutter GR , Hoffman HJ , Davis RO . Maternal serum alpha 2-macroglobulin and fetal growth retardation. Obstet Gynecol 1991;78:594-599.

27.

27. Neel NR , Goldenberg RL , Tamura T , Cliver SP , Avent K , Hoffman HJ . Maternal alpha-2-macroglobulin levels and fetal growth in Guatemala. Int J Gynaecol Obstet 1992;38:25-29.

28.

28. Kawser CA , Iredale JP , Winwood PJ , Arthur MJP . Rat hepatic stellate cell expression of α2-macroglobulin is a feature of cellular activation: Implications for matrix remodelling in hepatic fibrosis. Clin Sci 1998;95:179-186.